Which uncommon neurophysiological disorders cause abnormal integration of sensory, emotional, cognitive, and autonomic responses to neutral or specific stimuli, without involving psychosis, genetic syndromes, prion disease, neurodegeneration, brain injury, inflammation, infection, metabolic disorders, functional neurological disorder, or synesthesia?

Lesser-Known Neurophysiological Disorders with Abnormal Sensory-Emotional-Cognitive-Autonomic Integration

Based on the available evidence, the most relevant lesser-known neurophysiological disorders that fit your criteria are Sensory Modulation Disorder (SMD) and Complex Regional Pain Syndrome (CRPS) Type I, both of which demonstrate abnormal integration of sensory, emotional, cognitive, and autonomic responses to neutral or specific stimuli without involving the excluded conditions.

Primary Disorders to Consider

Sensory Modulation Disorder (SMD)

SMD represents a severe inability to regulate responses to everyday sensory stimulation that most people easily adapt to, affecting 5-16% of the general pediatric population 1. This disorder extends into adulthood and manifests as abnormal sensory-emotional-cognitive-physiological integration.

Two distinct phenotypes exist:

• Sensory Seeking/Hyperactive Subtype: Characterized by sensory craving, hyperactive and impulsive behavior, externalizing behaviors (delinquent, aggressive), unsocial patterns, inadaptive responses, and impaired cognitive/social functioning 1

• Sensory Withdrawal/Hyporesponsive Subtype: Characterized by movement sensitivity, emotional withdrawal, and low energy/weak behavioral patterns 1

Key distinguishing features:

• Affects multiple sensory domains simultaneously (touch, sound, light, movement)
• Creates hypersensitivity that becomes a maintaining factor, resulting in avoidant behaviors and limiting functional activities 2
• Produces physiological and somatic consequences without conscious emotional recognition (similar to "panic without panic" or alexithymia) 2
• Not classified as FND, though shares some overlapping features

Complex Regional Pain Syndrome (CRPS) Type I

CRPS Type I demonstrates profound abnormalities in central sensory-motor-autonomic integration pathways without requiring nerve injury 3.

Distinctive neurophysiological features:

• Abnormal Visual-Pain-Autonomic Integration: 61% of CRPS patients experience enhanced pain within seconds of viewing ambiguous visual stimuli (AVS), demonstrating abnormal pain networks interacting with central somatomotor and autonomic pathways 3

• Asymmetric Autonomic Responses: 33.5% of patients show asymmetric vasomotor responses to neutral visual stimuli, while all healthy controls demonstrate symmetric patterns 3

• Dystonic Reactions: 50% of patients with asymmetric vasomotor responses develop dystonic reactions in affected limbs when viewing neutral visual stimuli 3

• Diminished Baseline Vasoconstrictor Responses: Significant differences in sympathetic autonomic function between affected and unaffected limbs 3

Critical clinical point: These abnormal responses are not predictable from baseline autonomic function and represent central neuroplastic changes causing afferent sensory feedback conflicts 3.

Sensory Over-Responsiveness (SOR) in Adults

A specific adult manifestation of sensory processing dysfunction that warrants separate consideration 4.

Neurophysiological characteristics:

• Atypical Vagal Tone Reactivity: Women with SOR fail to demonstrate normal vagal tone withdrawal (measured by RMSSD) during challenging pain loads, while controls show expected parasympathetic withdrawal 4

• Reversed Stress-Autonomic Correlations: Higher anxiety and somatization correlate with shorter R-R intervals in SOR (indicating sympathetic dominance), while controls show the opposite pattern 4

• Multi-sensory Integration Dysfunction: Associated with psychological distress and hyperalgesia without structural pathology 4

Important Clinical Distinctions

What These Disorders Are NOT:

The evidence clearly excludes several categories you specified:

• Not Neurodegenerative: These lack progressive neuronal death characteristic of Alzheimer's, Parkinson's, or frontotemporal dementia 5, 6
• Not Genetic Syndromes: Unlike Hereditary Sensory and Autonomic Neuropathy (HSAN) which requires genetic mutations 7
• Not Prion Disease: No transmissible misfolded proteins 8
• Not Primary Psychiatric: Though psychiatric symptoms occur, the core pathology involves neurophysiological integration abnormalities
• Not FND: While sharing some features with FND (particularly hypersensitivity 2), SMD and CRPS have distinct diagnostic criteria and pathophysiology

Common Pitfalls to Avoid:

1. Misdiagnosing as purely psychiatric: The autonomic and sensory integration abnormalities are measurable and objective 3, 4

2. Overlooking the visual-autonomic connection: In CRPS, neutral visual stimuli can trigger pain and autonomic responses within seconds—this is a diagnostic clue 3

3. Assuming symmetry: Asymmetric autonomic responses to neutral stimuli are pathognomonic in certain CRPS presentations 3

4. Missing the developmental trajectory: SMD often begins in childhood but persists into adulthood with evolving phenotypes 1

Diagnostic Approach

For suspected SMD:

• Assess responses across multiple sensory domains (tactile, auditory, visual, vestibular)
• Identify behavioral phenotype (seeking/hyperactive vs. withdrawal/hyporesponsive)
• Document functional impairments in daily activities
• Rule out structural neurological pathology

For suspected CRPS Type I:

• Test autonomic responses using laser Doppler flowmetry during neutral visual stimuli exposure
• Assess for asymmetric vasomotor patterns between limbs
• Document pain responses to ambiguous visual stimuli
• Observe for dystonic reactions during sensory challenges
• Measure baseline sympathetic function (deep breath test)

For suspected SOR:

• Assess heart rate variability during graded sensory/pain challenges
• Evaluate vagal tone reactivity patterns
• Screen for anxiety and somatization with attention to autonomic correlations
• Document hyperalgesia and multi-sensory integration difficulties

These disorders represent genuine neurophysiological abnormalities in central integration pathways that produce complex symptom patterns without the structural, infectious, metabolic, or degenerative pathology you wished to exclude.